Skeletal muscle biopsies will be performed on 150 hospitalized, psychiatric patients (mostly acutely and chronically psychotic individuals), 40 first-degree relatives of acutely and chronically psychotic patients, 10-20 patients with acute organic brain diseases, and 30 normal controls over a 3 year period. The muscle biopsies will be examined with histochemical, phase optic and electron microscopic methods, to determine the nature and incidence of abnormalities of the muscle cell and neuromuscular junction in the various populations. Similar techniques will be utilized to examine the skeletal muscle of rats and rhesus monkeys treated with psychotomimetic drugs phencyclidine (phen) and methamphetamine, prior to restraint stress and other types of stress. Preliminary studies suggest this is an excellent model system for the muscle changes in psychotic patients. Other studies with this model will involve the use of various doses of each agent, pharmacologic inhibitors, adrenal demedullated rats, rats with prior denervation of the muscle to be examined, and rats with discrete brain lesions that may inhibit the increased in PCPK levels produced by phen or methamphetamine and restraint. The effects on rat skeletal muscle of other forms of stress or epinephrine with and without phen, prolonged administration of psychotropic drugs, Polymyxin B, Compound 48/80, physical activity and direct trauma will also be studied. Understanding the relationship between morphologic change and release of muscle enzymes into the circulation will be one of the aims of this study. The role of the nervous system in muscle pathology and release of enzymes from muscle will be further defined.